Molecular biology of keratinocyte differentiation

Epidermal keratinocytes (skin cells) are highly specialized epithelial cells designed to perform a very specific function, separation of the organism from its environment. To accomplish this the cells synthesize precursors and assemble them into two distinct structures, the cornified envelope and keratin intermediate filaments. The intermediate filaments are assembled from keratin monomers and the cornified envelope is assembled from a protein called involucrin and several other proteins. Expression of involucrin and the keratins genes are regulated as a function of the stage of keratinocyte differentiation and by various external agents such as calcium and vitamin A. To study the function of these structures and the regulation of precursor production we have cloned cDNA and genomic clones encoding involucrin and four of the keratin polypeptides. Retinoids profoundly alter the differentiation pattern of human epidermal keratinocytes, but the underlying biochemical basis of this change is not known. In this report we describe retinoid-promoted changes in keratin gene expression that may, in part, be responsible for the alteration in cellular phenotype in the presence of the vitamin. We also describe the novel structure of the human 40 kD keratin, a member of the keratin family that is retinoid responsive and is likely to be important during epidermal development. Finally, we describe the structure of the envelope precursor protein, involucrin, as determined from its DNA sequence and speculate on its role in cornified envelope formation.